Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interactions of ergot alkaloids and of other drugs with dopamine (DA) and alpha-adrenergic receptors were investigated. The tested ergot alkaloids inhibit synaptosomal tyrosine hydroxylase activity and reverse the apomorphine-elicited inhibition of synaptosomal tyrosine hydroxylase activity. Thus, ergot alkaloids interact as both agonists and antagonists with the presynaptic DA receptors. Ergot alkaloids also compete effectively for the binding of 3H-DA and 3H-haloperidol to bovine striatal membranes. These results show that these drugs are mixed agonist-antagonists with respect to the postsynaptic DA receptors. To determine the effects of ergot alkaloids and of neuroleptics on the alpha-adrenergic receptors in the CNS, we have measured their effects on the binding of 3H-dihydroergocryptine and 3H-WB-4101 to cerebral cortical membranes. The displacing potencies of the tested ergot alkaloids and of the neuroleptics indicated that they have a high affinity for the alpha-adrenoreceptors in the CNS. The mechanisms underlying the therapeutic efficacy of mixed agonist-antigonists of DA and alpha-adrenergic receptors in Parkinson's disease and in geriatric disorders were considered.
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PMID:Binding interactions of ergot alkaloids with monoaminergic receptors in the brain. 2 80

The mood-enhancing effects of fungi and their medicinal properties have been recognized for centuries. Ergot was initially used by midwives to speed childbirth in the Middle Ages. More recently their pharmacological action on dopamine receptors has been exploited to treat post-partum bleeding, migraine, Parkinson's disease and senile dementia. Further indications of the potential value of microbial metabolites are exemplified by the discovery and development of cyclosporin, to treat organ rejection, and mevinolin, a cholesterol-lowering drug. Such discoveries are not unexpected because we have known for some time that fungi regulate morphogenesis, differentiation and sexuality via hormonal molecules, ranging from peptides through to steroidal molecules similar in structure to human sex hormones. A combination of the power of molecular biology to design screens based on isolated disease mechanisms with the chemical inventiveness of microorganisms is providing numerous new pharmacophores for drug development.
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PMID:Useful functions of microbial metabolites. 130 79

Ergot derivatives have been proposed to have ameliorative effects in various pathological conditions where dopaminergic transmission is believed to be impaired, namely Parkinson's disease, amenorrhea-galactorrhea syndrome, and in the treatment of behavioural disturbances of the elderly. To get more insight into a possible involvement of a direct action of ergot derivatives on dopamine receptors we studied the effect of acute and chronic dihydroergotoxine (DHT) treatment on 3H-Spiroperidol and 3H-N-Propylnorapomorphine (3H-NPA) binding to rat striatal membrane preparations. The results are in favor of an interaction of ergot derivatives with dopamine recognition sites both after acute and chronic treatment.
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PMID:Chronic dihydroergotoxine treatment affects the number of dopamine recognition sites in rat striatum. 646 97

The occurrence of late side effects of long term levodopa therapy (fluctuations in motor performance, abnormal movements, and symptoms unresponsive to dihydroxyphenylalanine) led to the search for novel anti-Parkinsonian drugs. Dopamine agonists are one of the newer families of anti-Parkinsonian agents, and they include ergot derivatives and apomorphine, which can be used in the different stages of Parkinson's disease. Ergot derivatives (bromocriptine, lisuride, pergolide) are believed to act independently of the dying cells of the substantia nigra, acting instead directly on postsynaptic dopamine receptors in the striatum. They are usually used in combination with levodopa when late side effects occur, especially 'wearing-off' or decreased efficacy of levodopa. They can also be prescribed earlier in combination with levodopa in de novo Parkinsonian patients, and in this setting are thought to delay the occurrence of late adverse motor effects. In some patients, monotherapy with relatively high doses of ergot derivatives can be used as initial treatment. However, their efficacy often decreases after 1 to 3 years, thus justifying a late combination with levodopa. Apomorphine is a non-ergot derivative dopamine agonist, which is used subcutaneously for the treatment of severe 'off' refractory periods, in combination with other dopaminergic drugs without changing the patient's routine drug regimen.
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PMID:Current status of dopamine agonists in Parkinson's disease management. 769 30

All medications currently used to treat Parkinson's disease carry some risk of causing confusion, hallucinations, or disruption of such higher-order mental operations as problem-solving and learning. Although the elderly demented patient is at greatest risk, such complications have also been noted during treatment of younger patients. Treatment with anticholinergics may lead to a confusional state and decreased memory function in some patients, especially the elderly and those with preexisting dementia. Monoamine oxidase inhibition is considered quite benign when used alone, but may potentiate certain side effects when used in combination with other compounds. Ergot alkaloid medication, which is usually combined with levodopa, often induces severe psychiatric complications. Typical findings with levodopa treatment indicate little or no positive impact on cognition, apart from nonspecific arousal and alleviation of concomitant depressive affect. Guidelines for the management of neuropsychological and psychiatric side effects are suggested.
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PMID:Neuropsychological and psychiatric side effects in the treatment of Parkinson's disease. 826 12

Pramipexole, an amino-benzathiazole [(S)-4,5,6,7-tetrahydro-N-6-propyl-2, 6-benzothiazolediamine dihydrochloride monohydrate] direct-acting dopamine receptor agonist effective in treating Parkinson's disease, bound selectively and with high affinity to dopamine D2-like receptors, with highest affinity at dopamine D3 receptors. Ergot dopamine receptor agonists (bromocriptine, lisuride, pergolide) bound to both dopamine and non-dopamine receptors. Although all agonists depressed dopamine neuron firing, only pramipexole and quinpirole completely silenced firing when administered in slowly-accumulating doses. High-dose pergolide, but not other ergots, completely suppressed firing when given by a prompt bolus i.v. injection, suggesting efficacy limitations may have involved receptor desensitization for pergolide, but not for bromocriptine and lisuride. We conclude that pramipexole differs from ergot dopamine receptor agonists currently used in the treatment of Parkinson's disease by virtue of its selectivity for dopamine receptors, its preferential affinity for the dopamine D3 receptor subtype, and its greater efficacy for stimulating dopamine receptors, as indicated in these electrophysiology assays.
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PMID:Inhibition of dopamine neuron firing by pramipexole, a dopamine D3 receptor-preferring agonist: comparison to other dopamine receptor agonists. 889 76

Ergot alkaloids, such as ergotamine, have been associated with numerous vascular complications and with valvular heart disease. The authors describe a man who developed fibrosis of three heart valves during a 5-year treatment with bromocriptine for Parkinson disease. There were no other plausible causes. To our knowledge, such a side effect has never been described with this drug.
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PMID:Fibrotic valvular heart disease subsequent to bromocriptine treatment. 1239 Jun 88

(1) Ergot derivatives are used for a variety of indications, including migraine, Parkinson's disease, endocrine disorders, and cognitive and neurosensory deficits in elderly people. (2) Fibrosis is a common complication of treatment with ergot derivatives. (3) Retroperitoneal fibrosis is the commonest form. Pleuropulmonary and pericardial fibrosis also occur. (4) Cardiac valve damage has been linked to some ergot derivatives. (5) Fibrosis occurs during long-term treatment. (6) Renal, pulmonary and cardiac complications can be serious. The fibrosis is often reversible if the drug is stopped quickly. (7) In practice, this risk of serious adverse effects tips the scales against these drugs for poorly established indications such as cognitive and neurosensory deficits in elderly people. The possibility of drug induced fibrosis should be considered at the first sign of renal, cardiac or pulmonary fibrosis in a patient on ergot derivatives.
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PMID:Fibrosis due to ergot derivatives: exposure to risk should be weighed up. 1247 1

Dopamine agonists are increasingly being used in the initial treatment of patients with de-novo Parkinson's disease because they provide symptom relief and a low risk of the dyskinesia frequently associated with levodopa. Evidence is also mounting in preclinical models that dopamine agonists protect dopaminergic neurons from the toxic effects of oxidative stress and the by-products of dopamine and L-dopa metabolism. Ergot derivatives, such as pergolide, induce minor side-effects and provide significant and sustained improvements in motor function in patients with early Parkinson's disease. Dopamine agonists also appear to reduce the loss of functional dopamine transporters when used early in the disease course, and these factors combine to build a case for the use of dopamine agonists in early-stage Parkinson's disease.
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PMID:Rationale for dopamine agonist use as monotherapy in Parkinson's disease. 1518 Jan 35

Ergot derivative dopamine agonists, e.g. pergolide, bromocriptine, dihydroergocriptine used in treatment of Parkinson's disease can cause pleural, pericardial, retroperitoneal and valvular fibrotic changes. Case No 1: A 56-year-old woman with PD was treated with pergolide 3mg/24h since July 2002. In June 2003, edema of lower extremities was first noticed and echocardiography found a minor mitral regurgitation without any morphological changes of the valve. In January 2004, left- sided cardiac failure rapidly developed and echocardiography revealed multivalvular insufficiency with predominating severe mitral regurgitation. Mitral valve replacement was performed and pergolide was changed to ropinirole. Until now, neither cardiac functions nor motor status are sufficiently compensated. Case No 2: A 66-year-old-man with PD since 1996 was treated with pergolide 3 mg/day since 1999. In the beginning of 2004, leg edema appeared. On examination, bilateral hydronephrosis with ureteric strictures and incipient renal insufficiency was found. Bilateral ureteroplasty was performed and the histology showed periureteric fibrosis. Treatment with steroids was initiated and pergolide was changed to pramipexole. Despite the treatment, the fibrosis progressed, requiring ureteral stenting. Based on the literature review and on our own experience, we propose following guidelines to minimize the risk of complications: A. Not to use EAD as the first-line dopamine agonists. B. Regularly follow all patients treated with EAD, especially monitor the majorsymptoms: dyspnea, cough, fatigue, leg edema (also asymmetric), symptoms of urinary outflow obstruction, cardiac insufficiency, chest pain, heart murmur. An elevated ESR, C-reactive protein or anemia support the diagnosis. C. All symptomatic patients should undergo workup for serosal fibrosis (according to type of complication): chest X-ray or CT scan, spirometry, renal functions, renal ultrasound, CT of retroperitoneum. D. Before the introduction of EAD therapy, examine the renal functions, perform chest X-ray and echocardiography. Screening echocardiography should be performed in 3-6 months and subsequently in every 6-12 months.
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PMID:[Organ changes induced by ergot derivative dopamine agonist drugs: time to change treatment guidelines in Parkinson's disease?]. 1580


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